CLINICAL CORE PROJECT SUMMARY/ABSTRACT The mission of the Clinical Core parallels that of the MADRC as a whole: To support research into the causes, mechanisms and treatment of AD and related dementias, with the eventual goal of curing and even preventing these disorders. When first established in 1984, much of our work centered on AD, beginning with AD dementia and expanding to Mild Cognitive Impairment (MCI). The focus broadened over the past 5 years as investigators in the Core developed specific research programs in vascular cognitive impairment, Parkinson disease dementia/dementia with Lewy bodies, and frontotemporal dementia. We now expand our Core's focus further to emphasize the behavioral and biological features of normal elders at risk for dementia and those with subjective cognitive concerns. In order to facilitate clinical research in these areas, we have established and maintain a Longitudinal Cohort (LC) of men and women from diverse ethnic and racial backgrounds spanning a full range of cognitive function from normal to subjective complaints to MCI to dementia. Comprehensive and systematic examination of this cohort is central to the Clinical Core mission. From this well-characterized and longitudinally followed cohort, we provide timely and accurate data submission to NACC; subjects for national multi-center studies such as ADNI, DIAN and ADCS trials; and biological samples for genetic and biomarker research. The LC also fuels our Center's local research studies: we will continue to support the more than 40 studies that rely on our evaluations and our subjects, their data and/or their biologic fluids for success, including Projects 1 and 2 in this renewal application. A special emphasis of our Core, in line with our Center's theme of understanding and recognizing the earliest phase of disease, is the development of novel assessment tools that can be used in our and others' studies in this area. We will also work on referring subjects to the new Neuroimaging Core, on supporting the new Recruitment Registry in the Outreach Core, and on coordinating with the Neuropathology Core to facilitate smooth autopsy protocols. The Core will join with the Outreach Core in raising awareness about AD and dementias, and assist in increasing the number of minority subjects who have access to LC and research projects. A final goal of the Core is help train the next generation of investigators, and we will continue to attract promising clinician-scientists and provide a stimulating environment for their career development.